Integrated Sensor for Analyzing Biological Samples

ABSTRACT

An integrated lancet and testing striplet for measuring a body analyte level in a health care regimen includes a skin piercing member and an analyte sensor coupled together.

PRIORITY

This application claims the benefit of priority to U.S. provisionalpatent application No. 60/741,019, filed Nov. 30, 2005, which is herebyincorporated by reference. This application is related to acontemporaneously-filed application entitled Integrated Meter forAnalyzing Biological Samples by the same Assignee.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to the field of medical diagnostic devices.

2. Discussion of the Related Art

The prevalence of diabetes is increasing markedly in the world. At thistime, diagnosed diabetics represent about 3% of the population of theUnited States. It is believed that the actual number of diabetics in theUnited States is much higher. Diabetes can lead to numerouscomplications, such as, for example, retinopathy, nephropathy, andneuropathy.

The most important factor for reducing diabetes-associated complicationsis the maintenance of an appropriate level of glucose in the bloodstream. The maintenance of the appropriate level of glucose in the bloodstream may prevent and even reverse some of the effects of diabetes.

Glucose monitoring devices known in the art have operated on theprinciple of taking blood from an individual by a variety of methods,such as by means of a needle or a lancet. The individual then contacts astrip carrying reagents with the blood, and finally inserts the stripinto a blood glucose meter for measurement of glucose concentration byoptical or electrochemical techniques.

Medical devices of the prior art for monitoring the level of glucose inthe blood stream have required that an individual have separatelyavailable a needle or a lancet for extracting blood from the individual,test strips carrying reagents for bringing about a chemical reactionwith the glucose in the blood stream and generating an optical orelectrochemical signal, and a blood glucose meter for reading theresults of the reaction, thereby indicating the level of glucose in theblood stream. The level of glucose, when measured by a glucose meter, isread from the strip by an optical or electrochemical meter.

It is desired to simplify the systems, devices, and methods fordetermining the level of an analyte such as glucose in a body fluid suchas blood. In particular, it is desired to integrate the operations ofextracting a sample of blood by means of a needle or a lancet, applyingthe sample of blood to a reagent-bearing test strip, reading the resultof a glucose monitoring test, and discarding the used needle or lancetand test strip in a safe and efficient manner.

Certain patents describe devices that can perform steps for determiningthe concentration of glucose in the blood stream. For example, U.S. Pat.No. 5,632,410 discloses a sensor-dispensing instrument for handling aplurality of fluid sensors (i.e., test strips). However, this patentfails to include a lancing device for puncturing the skin of a patientin order to extract a sample of blood. U.S. Pat. No. 6,908,008 disclosesan apparatus that includes a dispenser comprising a housing having achamber; a means for retaining a plurality of test strips in asubstantially moisture-proof, air-tight first position; and a means foropening the chamber and moving one of the plurality of test stripstranslationally from a first position inside of the chamber to a secondposition at least partially outside of the chamber, wherein the openingof the chamber and the moving of the one test strip is achieved by asingle mechanical motion; and an electrochemical analyzing means foranalyzing a biological fluid. However, like, U.S. Pat. No. 5,632,410,this patent fails to simplify the testing process, e.g., this patentfails to include a lancing device for puncturing the skin of a patientin order to extract a sample of blood.

U.S. Pat. No. 5,035,704 discloses a blood sampling mechanism including atest pad of a predetermined thickness set-off between oppositerelatively closely spaced surfaces imparting a thin configuration tosaid test pad, said test pad carrying a dermis-piercing member having apointed end, said pointed end being disposed inboard of said oppositesurfaces, means for applying a force to said dermis-piercing member in adirection to move said pointed end beyond one of said opposite surfacesto pierce the dermis and thereby obtain a blood sample, means fortesting the blood sample, means for defining a blood sampling station atwhich the blood sample is obtained, means for defining a blood testingstation at which the blood sample is tested by said blood sample testingmeans, and means for conveying said test pad from said blood samplingstation after the blood sample has been obtained to said blood testingstation. The dermis-piercing member and test pad are, however, entirelyseparate components in this system (see also WO 03/082091). U.S. Pat.No. 5,971,941 discloses a blood sampling apparatus for sampling bloodfrom the skin of a patient for analysis. The apparatus includes acartridge and a housing with a driver. The cartridge has a cartridgecase, lancet, and a compartment associated with the cartridge case forreceiving blood. The lancet is housed in the cartridge case andoperatively connected thereto such that it is drivable to extend outsidethe cartridge case through a lancing opening for lancing the skin toyield blood. The housing has a driver for urging the lancet to extendoutside the cartridge case. During lancing, the cartridge may bedetachably held in the housing such that the cartridge can bedisassociated from the driver after sampling blood. The U.S. Pat. No.5,971,941 discloses that material around a lancet aperture in acartridge case soaks up blood after lancing (see also U.S. Pat. No.5,279,294). This does not bring the absorbent material to the center ofthe sample, and when only a small amount of blood is available such asis often the case in alternate site testing away from fingertips, thentesting may be unreliable, may need to be repeated far too often, or maysimply require testing at the fingertips. Application of sample fluid toa capillary end leading to reagent material involves careful manualalignment. A manual actuation step is also involves in getting thelancet to protrude from the cartridge.

WO 2004/041082 discloses a device for use with a body fluid samplingdevice for extracting bodily fluid from an anatomical feature. Thedevice comprises a cartridge having a plurality of cavities. The devicemay include a plurality of penetrating members each at least partiallycontained in the cavities of the cartridge wherein the penetratingmembers are slidably moved to extend outward from openings on thecartridge to penetrate tissue. The device may also include a pluralityof analyte detecting members and a plurality of chambers. Each chambermay be associated with one of the cavities, the chambers positionedalong an outer periphery of the cartridge, wherein at least one of theanalyte detecting members forms a portion of one wall of one of theplurality of chambers.

U.S. Pat. No. 6,352,514 discloses a body fluid sampling device thatincludes a lancet and a test strip. The lancet is disposed on a lancetcarrier, while the test strip is disposed at the end of a capillarytube. Body fluid exposed at a lancing site is drawn up into a capillarytube which is placed into contact with the body fluid. At the end of thecapillary tube is a test strip. Once the body fluid is drawn up thecapillary tube, it may be applied to the test strip to determine ananalyte level. The lancet and the capillary tube and test strip arecontained within a same sampling device housing, although they areconfigured as two separately disposable items and not integratedtogether as a single item. These items are separately manipulated into,within and out of the housing before, during and after use,respectively.

It would be desirable to develop a test sensor that also serves as alancet for forming an opening in the skin of a patient to enable asample of biological liquid to emerge from the patient, so that thesample of bodily fluid may be collected from the patient emerging fromthe opening in the skin by a test strip, and analyzed to determine acharacteristic of the bodily fluid. It would also be desirable todevelop a medical diagnostic device that is small in size, reliable touse, and provides accurate results, even when only a small volume ofsample of biological liquid is collected.

SUMMARY OF THE INVENTION

Integrated lancet and testing sensors (“striplets”) are provided formeasuring a body analyte (e.g., glucose) level in a health care (e.g.,diabetes) regimen. A lancet body includes a sensor receiving end and alancet end. A lancet needle is coupled with and protruding from thelancet end. An optional lancet cap may secure the lancet. A sensor iscoupled to the test strip receiving end of the lancet body havingmultiple electrodes and assay chemistry for testing an analyte (e.g.,glucose) level of an applied body fluid. In certain embodiments, thetest strip and lancet needle are relatively disposed at different endsof the striplet for providing both lancing and application of body fluidat a lancing site by reorienting and advancing the striplet within themeter after lancing to contact a sample receiving portion of the teststrip precisely at the lancing site.

In certain embodiments, a striplet includes both a test strip portionand a lancet portion. These may be relatively opposed, e.g., extendingabout 180 degrees from each other, or extending at another angle fromzero to 360 degrees. The lancet portion may couple to the test stripportion as a two-piece device, or each may couple with a lancet body asa three-piece device.

The reorienting may include rotating the striplet when the lancing siteremains approximately at the predetermined location relative to themeter for application of body fluid to the sample receiving portion ofthe test strip. In certain embodiments, the test strip and lancet aresymmetrically disposed at opposite ends of the lancet body. Thereorienting may include rotating and/or flipping the striplet when thelancing site remains approximately at the predetermined locationrelative to the meter for application of body fluid to the samplereceiving portion of the test strip.

The lancet body may include a pair of relatively disposed recesses forrespectively positioning the test strip via a latching mechanism orspring-loaded ball and detent mechanism for lancing and application ofbody fluid at a same lancing/testing site. The recesses may betrapezoidally-shaped, or another suitable shape.

Embodiments may include a lancet cap. A lancet cap may include one ormore elastomeric arms that couple with defined cutouts in the lancetbody for snapping the cap into and out of mating relationship with thelancet body by respective application of sufficient coupling andseparation force.

The lancet body and test strip may include at least two teeth that fitcorresponding slots for coupling the lancet body and test striptogether, and the lancet body has the teeth and the test strip has thecorresponding slots.

The test strip may include one or more substrates, e.g., may include afirst substrate (e.g., a base) and a second substrate (e.g., a cover).The first substrate may have a layer of electrically conductive materialapplied to one major surface thereof, while the second substrate mayhave a working electrode (and optionally a trigger electrode) applied toat least one major surface thereof. Electrodes may be coplanar or may bedisposed on different surfaces or be opposed. The first substrate may beadhered to the second substrate by a layer of electrically conductiveadhesive and/or a layer of non-conductive adhesive.

The sensor-containing portion may include a sample flow channel, and aworking electrode and optional trigger electrode may be positioned inthe flow channel.

The cover may include at least one electrical passageway running from aninner face to an outer face and/or a slot formed therein to attach thesensor-containing portion to a tab in the lancet-containing body.

The base may include an opening formed therein to attach thesensor-containing portion to a tab in the lancet-containing body.

In certain embodiments, the base or the cover may include a recessformed in an edge thereof that forms the sample receiving portion of thetest strip. The recess may have a hydrophilic material applied thereto.The lancet may be positioned approximately 180° from the recess.Electrical contact pads may be on one major surface of the cover and/orbase. The cover and/or trigger electrode may include a layer ofelectrically conductive or semiconductive material, and may includecarbon.

Methods of providing a sample of body fluid to a test strip formeasuring an analyte level within the fluid are also provided.Embodiments of the subject methods include providing an integratedanalyte testing striplet and within a metering chamber, and piercing alancing site with the lancet needle at a predetermined location relativeto the meter. In certain embodiments, the striplet is automaticallyreoriented and advanced within the meter including contacting withprecision a sample receiving portion of the test strip at the lancingsite, such that body fluid from the lancing site is applied to thesample receiving portion of the test strip for measuring a level.

The method may also include disarming the lancet needle and disposing ofthe testing striplet. The lancing site may remain approximately at thepredetermined location relative to the meter when body fluid is appliedto the sample receiving portion of the test strip. The reorienting mayinclude rotating and/or flipping the striplet. The loading may includemating a first recess defined within the lancet body with a latchingmechanism or a ball and detent mechanism of the glucose meter, such thatthe test striplet is specifically disposed at a lancing orientation. Thereorienting may then include mating a second recess defined within thelancet body with the same latching or ball and detent mechanism, suchthat the testing striplet is specifically disposed at a testingorientation. The recesses may be trapezoidally-shaped, or anothersuitable shape.

The arming may include uncoupling a lancet cap by uncoupling one or moreelastomeric arms of the lancet cap from defined cutouts in the lancetbody by application of sufficient separating force. The disarming of thelancet needle may involve snapping the one or more elastomeric arms ofthe lancet cap back into mating relationship with the defined cutouts ofthe lancet body by application of sufficient coupling force.

The method may include coupling at least two teeth that fitcorresponding slots for coupling the lancet body and test striptogether. The lancet body may have the teeth, while the test strip hascorresponding slots.

In another embodiment, a test strip includes a lancet-containing portionand a sensor-containing portion. During a time that the test strip isstored in a medical diagnostic device, a protective cover encloses thelancet of the lancet-containing portion. The medical diagnostic deviceis capable of removing the protective cover to enable the lancet to forman opening in the skin of the patient and is further capable ofre-attaching the protective cover onto the lancet to enable the medicaldiagnostic device to eject the used test strip in a safe manner.

In the case of collection of an inadequate quantity of sample, themedical diagnostic device enables re-lancing. The test sensor mayrequire only a small volume of sample to carry out a complete test suchas sub-microliter sample volumes, e.g., 0.5 microliter or less, or 0.3microliter or less, or 0.2 microliter or less in certain embodiments.The test strip combines a lancet and a sensor in a single small unit.After the skin of the patient is pierced and a sample of biologicalliquid, e.g., blood, appears, the test strip is moved into position forcollecting a sample of the liquid, and the liquid enters the sampleapplication zone of the sensor-containing portion of the test stripwithout manipulation of the test strip by the user.

An integrated lancing and testing kit is also provided for measuring abody analyte level in a health care regimen. The kit includes a meterfor analyzing the analyte to determine the body glucose level, and acartridge containing one or more integrated lancet and testingstriplets. The striplets include features described above and belowherein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded perspective view of an assembly for storing anddispensing test strips in accordance with a preferred embodiment.

FIG. 2 is an exploded perspective view of selected components of thelancing/collecting assembly of a medical diagnostic device including anintegrated lancet and testing striplet in accordance with a preferredembodiment.

FIG. 3 is another perspective view of selected components of thelancing/collecting assembly of a medical diagnostic device illustratingentry of an integrated lancet (with cover) and testing striplet inaccordance with a preferred embodiment.

FIG. 4A is a partially-exploded, perspective view of one embodiment ofan integrated lancet and testing striplet, showing a lancet bearing aremovable protective cover.

FIG. 4B illustrates another embodiment of an integrated lancet andtesting striplet.

FIG. 5 is a perspective view of the sensor-containing portion of theembodiment of the test strip shown in FIG. 4.

FIG. 6A is an exploded perspective view of the sensor-containing portionof the test strip shown in FIG. 5. In this view, the recesses for tabsof the lancet-containing portion of the test strip are not shown.

FIG. 6B illustrates the sensor-containing portion of FIG. 6A includingan end fill strip with a hydrophilic end fill recess in accordance witha preferred embodiment.

FIG. 7A is a perspective view of the inner face of the cover of thesensor-containing portion of the test strip shown in FIG. 4. In thisembodiment, recesses for tabs of the lancet-containing portion of thetest strip are illustrated.

FIG. 7B is a perspective view of the inner face of the base of thesensor-containing portion of the test strip shown in FIG. 4.

FIG. 7C is a perspective view of the test strip of FIG. 4 inserted intoan analyzer of a medical diagnostic device in accordance with apreferred embodiment.

FIG. 8A is a perspective view of the inner face of the cover of anotherembodiment of the sensor-containing portion of the test strip.

FIG. 8B is a perspective view of the inner face of the base of thesensor-containing portion of the test strip illustrated in FIG. 8A. Inthis embodiment, the openings for tabs of the lancet-containing portionof the test strip are shown.

FIG. 8C is a perspective view of the test strip made from the base shownin FIG. 8A and the cover shown in FIG. 8B inserted into an analyzer of amedical diagnostic device in accordance with a preferred embodiment.

FIG. 9 is an exploded perspective view of another embodiment of the teststrip, showing a lancet bearing a removable protective cover.

FIG. 10 illustrates a sensor containing portion of a test strip.

FIGS. 10A-10B illustrate a lancet body with a test strip coupled theretoand a lancet body for coupling a test strip thereto in accordance withpreferred embodiments.

FIG. 11 is an exploded perspective view of the sensor-containing portionof the test strip shown in FIG. 9.

FIG. 12 is a flow chart illustrating the operations of a medicaldiagnostic device involving an integrated lancet and testing striplet inaccordance with a preferred embodiment.

FIGS. 13A-13M are schematic views illustrating positions of alancing/collecting assembly during one cycle of operation of a medicaldiagnostic device in accordance with a preferred embodiment.

DETAILED DESCRIPTION

As used herein, the expressions “storing/dispensing assembly” and“assembly for storing and dispensing test strips” means a mechanism thatis capable of both (a) storing a plurality of test strips in a magazineand (b) advancing the test strips, one at a time, from the magazine tothe lancing/collecting assembly. The expression “lancing/collectingassembly” means a mechanism that is capable of both (a) forming anopening in the skin of a patient and (b) collecting a sample ofbiological liquid emerging from that opening.

In addition, glucose is referred to in many places herein as arepresentative analyte. However, other analytes include glucose,lactate, and the like, in a body fluid. Additional analytes that may bedetermined include, for example, acetyl choline, amylase, bilirubin,cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB),creatine, DNA, fructosamine, glucose, glutamine, growth hormones,hormones, ketones, lactate, peroxide, prostate-specific antigen,prothrombin, RNA, thyroid stimulating hormone, and troponin. Theconcentration of drugs, such as, for example, antibiotics (e.g.,gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs ofabuse, theophylline, and warfarin, may also be determined. Any of theseanalytes may be used and glucose is used throughout as a representativeanalyte for convenience only and is in no way intended to limit thescope of the invention.

Medical Diagnostic Device

In one embodiment, a medical diagnostic device is provided that carriesout the functions of:

-   -   (a) storing a plurality of lancets and sensors;    -   (b) feeding a plurality of lancets and sensors to a system that        employs a lancet to form an opening in the skin of a patient and        then employs the sensor to collect a sample of biological liquid        that emerges from the opening formed in the skin;    -   (c) forming an opening in the skin of the patient by means of        the lancet;    -   (d) collecting the sample of biological liquid emerging from the        opening formed in the skin of the patient by means of the        sensor;    -   (e) analyzing the sample of biological liquid collected by the        sensor; and    -   (f) ejecting the used lancet and the used sensor in a safe        manner.

In another embodiment, a lancing/collecting assembly is provided thatreceives the test strip that includes the lancet-containing portion andthe sensor-containing portion. By means of various operations, thelancing/collecting assembly can perform one or more of the following:(a) orient the lancet-containing portion of the test strip in such amanner that the lancet of the lancet-containing portion of the teststrip can be advanced toward the skin of the patient in order to form anopening therein, (b) arm the lancet of the lancet-containing portion ofthe test strip, (c) trigger the armed lancet of the lancet-containingportion of the test strip so that the lancet forms an opening in theskin of the patient, (d) orient the sensor-containing portion of thetest strip in such a manner that the sensor-containing portion of thetest strip can be advanced toward the opening formed in the skin of thepatient to collect a sample of biological liquid emerging from theopening in the skin of the patient, and (e) advance the sensor of thesensor-containing portion of the test strip so that sufficient quantityof the sample of biological liquid can be collected for analysis todetermine a parameter of the biological liquid.

The lancing/collecting assembly is also capable of incorporating ananalyzer that is capable of analyzing the sample of biological liquidcollected from the opening in the skin of the patient.

In another embodiment, a method is provided for using the medicaldiagnostic device, including:

-   -   (a) feeding one of a plurality of test strips, each of the test        strips comprising a lancet-containing portion and a        sensor-containing portion to a lancing/collecting assembly that        employs a lancet of the lancet-containing portion to form an        opening in the skin of a patient and then employs a sensor of        the sensor-containing portion to collect a sample of biological        liquid that emerges from the opening formed in the skin;    -   (b) forming an opening in the skin of the patient by means of a        lancet in the lancet-containing portion;    -   (c) collecting a sample of biological liquid emerging from the        opening formed in the skin of the patient by means of the sensor        of the sensor-containing portion;    -   (d) analyzing the sample of biological liquid collected by the        sensor of the sensor-containing portion; and    -   (e) ejecting the used test strip in a safe manner.

As illustrated at FIG. 1, an assembly for storing and dispensing teststrips 110 includes a magazine for storing multiple test strips “TS”,each test strip including a lancet-containing portion and asensor-containing portion. Test strips that are suitable for use withthe medical diagnostic device of this invention are illustrated in FIGS.4-11, inclusive, and described in detail in the text accompanying thosefigures. The assembly 110 includes an exterior cover 120. The purpose ofthe exterior cover 120 is to maintain the test strips in a substantiallymoisture-tight, air-tight condition. A variety of materials are suitablefor forming the exterior cover 120 and include rubber and otherpolymeric materials, and the like. A platform 124 is for containing abiasing element 125, e.g., a constant force spring, for urging teststrips toward the location in the magazine 118 from which test stripsare fed to the lancing/collecting assembly. An insert 126 is forsecuring the biasing element 125. The platform 124 may be filled with adesiccant, in order to enhance moisture resistance of the test stripsstored within the assembly 110. Below the magazine 118 is a test striptrack 128 for providing a guide path for a test strip when the teststrip is being fed to the lancing/collecting assembly. The test striptrack 128 also abuts against a seal 130 attached to the bottom end ofthe assembly 110. The seal 130 surrounds the bottom end of the magazine118 and is typically made from a substantially air-impermeable,moisture-impermeable material, such as, for example, rubber or apolymeric material, or the like. The combination of the test strip track128 and the seal 130 provides a substantially moisture-tight, air-tightseal for the assembly 110.

Referring now to FIGS. 2 and 3, a first embodiment of alancing/collecting assembly 112 includes a cradle 280. The cradle 280holds a test strip during both the lancing step and the samplecollecting step, which are carried out by the medical diagnostic device.The cradle 280 also orients a test strip for lancing, and reorients thetest strip for sample collecting, so that the lancet of thelancet-containing portion of the test strip can form an opening in theskin of the patient during lancing and the sensor of thesensor-containing portion of the test strip can collect the sample ofbiological liquid emerging from the opening in the skin of the patientduring sample collecting, e.g., without manual intervention. In theembodiment shown in FIGS. 2 and 3, the cradle 280 also holds the teststrip during analyzing. The cradle 280 includes two upright members 282and 284 and a transverse member 286. The transverse member 286 of thecradle 280 connects the two upright members 282 and 284 of the cradle280. The upright member 282 of the cradle 280 has a slot 288 formedtherein, and the upright member 284 of the cradle 280 has a slot 290formed therein. The slots 288 and 290 receive an L-shaped element 292and 294, respectively, formed on a carrier 296. The L-shaped element 294has a foot 294 a and a leg 294 b. The L-shaped element 292 also has afoot and a leg which are not shown. The foot 294 a of the L-shapedelement 294 is capable of sliding in the slot 290 (and correspondinglyfor element 292 and slot 288) of the cradle 280 during lancing andsample collecting, so that the lancet of the lancet-containing portionof the test strip can form an opening in the skin of the patient duringlancing and the sensor of the sensor-containing portion of the teststrip can collect the sample of biological liquid emerging from theopening in the skin of the patient during collecting. The sliding motionof the foot 294 a is brought about by the movement of a cam follower 274during lancing and during sample collecting.

The carrier 296 houses the electrical components and electroniccomponents for completing a circuit when the test strip has received asample of biological liquid from the patient. FIGS. 2 and 3 illustratehow the carrier 296 receives and holds a test strip. Examples ofelectrical and electronic components of the carrier 296, and types ofanalyses that can be performed by the carrier 296 are described indetail in U.S. Pat. Nos. 6,299,757 and 6,616,819.

Referring now to FIGS. 2 and 3, the lancing/collecting assembly 112includes a transmission system, and may include multiple gears forperforming one or more of: (1) enabling operation of components requiredfor a lancing operation for forming an opening in the skin of a patient,(2) collecting the sample of biological liquid emerging from the openingin the skin of the patient formed by the lancing operation, and (3)positioning a test strip during the analyzing operation. Otherconfigurations of gears, racks, can be used in place of theconfiguration shown in FIGS. 2 and 3. Transmission systems that utilizecomponents other than gears may be used. The transmission system of thelancing/collecting assembly includes gears shown in FIGS. 2 and 3, andmay be replaced in whole or in part by subsystems involving one or moreracks and one or more pinions. In certain embodiments, cam follower 274can be effected in two directions, the directions being separated byapproximately 180°, and the cradle 280 or equivalent can be capable ofbeing rotated approximately 180° from a first position to a secondposition, the first position and the second position being separated byapproximately 180°. As used herein, the expression “approximately 180°”means an angle ranging from about 160° to 200°, with angles being closeto 180° in many embodiments. In alternative embodiments, the directionsmay be any angle depending on the configuration of the medicaldiagnostic device and the relative locations of the lancet and testingstrip portions of the integrated lancing and testing striplet. Forexample, the lancet needle and testing striplet could protrude from alancet body at other than about 180 degrees from each other, e.g., about90 degrees or about zero degrees.

Devices for mechanical transmission of power, or “mechanisms”,constitute the basic units from which all kinds of devices are built.Every mechanism includes individual elements whose movements in relationto one another are “positive”, i.e., the motion of one element producesan accurately determinable and definable motion of every individualpoint of the other elements of that mechanism. Numerous combinations andmodifications are possible, and a few illustrative types of mechanismsare noted here:

-   -   (1) Screw mechanism: When a screw spindle is rotated, the        element attached to the nut will move in the longitudinal        direction of the screw. Conversely, if the nut is rotatably        mounted in the frame of the mechanism and driven, the screw        spindle will move longitudinally.    -   (2) Linkage or crank mechanism: The characteristic element is        the crank, which is rotatably mounted on a frame and is usually        so designed that it can perform complete revolutions. Its motion        is transmitted through the coupler (or connecting rod) to the        lever (or rocker arm), likewise rotatably mounted, but not        performing complete revolutions. Alternatively, instead of being        connected to a lever, the coupler may be attached to a sliding        element—e.g., a piston.    -   (3) Pulley mechanism: Connection between pulleys on their        respective shafts is effected by flexible elements (belts,        ropes).    -   (4) Ratchet mechanism: This serves to arrest a motion or to        produce an intermittent rotation in the driven element. The pawl        allows the ratchet wheel to rotate in one direction only,        preventing rotation in the opposite direction by engaging the        specially shaped teeth on the wheel.    -   (5) Gear mechanism: This type of mechanism, which is used        extensively herein, transmits rotary motion from one shaft to        another, usually in conjunction with a change in rotational        speed and torque. In a gear mechanism of the usual type, the        transmission is effected by the meshing of gear teeth, but in a        friction-gear mechanism, this positive drive is replaced by        frictional contact of wheels or rollers.    -   (6) Cam mechanism: This type of mechanism, which is used        extensively herein, involves a cam mounted on a frame. The cam        is driven and thereby moves a follower, which performs a desired        predetermined motion depending on the shape of the cam.        Further information relating to the foregoing mechanisms can be        found in “The Way Things Work”, Volume 2, Simon and Schuster        (New York: 1971), pages 198-217, incorporated herein by        reference.

With respect to the interaction between the cradle 280, the carrier 296,the L-shaped elements 292 and 294, the lancet-containing portion of thetest strip, and the sensor-containing portion of the test strip, thelancet of the lancet-containing portion of the test strip is movedtoward the skin of the patient to form an opening in the skin of thepatient. After an opening is formed in the skin of the patient duringthe lancing step, and after the lancet-containing portion of the teststrip is retracted, the test strip is oriented so that thesensor-containing portion of the test strip can collect a sample ofbiological liquid, e.g., blood, emerging from the opening in the skin ofthe patient.

In certain embodiments of the lancing/collecting assembly, themechanical transmission system orients the test strip by rotating thecradle 280 approximately 180° (when the sensor and lancet protrudeapproximately 180° from the lancet body, see FIG. 4), so that thesensor-containing portion of the test strip faces the opening in theskin of the patient. Unlike lancing, no arming or triggering isinvolved. However, the test strip moves in the same manner as it didduring the lancing, even though it is reoriented for testing instead oflancing, thereby enabling the sensor of the sensor-containing portion ofthe test strip to contact the sample of biological liquid emerging fromthe opening in the skin of the patient. The sensor of thesensor-containing portion of the test strip receives a sufficientquantity of the sample to carry out a determination of the analyte. Inan embodiment of a lancing/collecting assembly, the carrier 296 may bedesigned to carry out the determination of the analyte. During the assayor after the completion of the assay, the cradle 280 may be rotated,e.g., about 90°, by the mechanical transmission system to position thetest strip for re-attaching the protective cover to the used lancet ofthe lancet-containing portion of the test strip, removing the used teststrip from the lancing/collecting assembly, and disposing of the usedtest strip through an ejection port in a housing (not shown).

The medical diagnostic device can include a mechanism for ejecting usedtest strips from the cradle 280. This mechanism may be operated byemploying a user-actuated pushing assembly or a motor-actuated pushingassembly to push a used test strip out of the cradle 280 and out of theejection port of the housing.

To operate the lancing/collecting assembly, a motor can be used to applya rotating drive input. Alternatively, any rotating drive source couldbe used, e.g., manual input by the user.

Further detailed description of the medical diagnostic device is foundat contemporaneously filed application which is assigned to the sameassignee, and at the priority provisional application identified hereinabove.

Test Strips

As noted above, novel sensors (“striplets”) are provided. The stripletsmay be used with the medical diagnostic devices described herein, orother suitable devices. An embodiment of a striplet is shown in FIG. 4A,which shows test striplet 1000 has a sensor-containing portion 1002 anda lancet-containing portion 1004. In one embodiment, thesensor-containing portion 1002 includes a first substrate 1006 (a base)and a second substrate 1008 (a cover). FIG. 4B illustrates anotherembodiment of an integrated lancet and testing striplet 1000, includinga sensor-containing portion 1002 and a lancet-containing portion 1004each coupled to a lancet body 1202. The lancet containing portionincludes a lancet 1200 shown protected by an optional elastomer cover1204 in FIG. 4B. The elastomer cover 1204 includes a pair of arms 1003that are configured to fit with corresponding cut-outs in the lancetbody 1202, so that the cover 1204 can be slipped on and off byapplication of sufficient coupling and separating force, respectively.

The lancet body includes sides 1203 that are symmetric and may besubstantially identical. Each side 1203 is mostly flat like the walls ofa tray of carrier 280 (see FIGS. 2 and 3), yet include a recess 1205that is suitably shaped, e.g., trapezoidally-shaped, or the like. Therecesses 1205 are for coupling with a mating mechanism, e.g., a latchingmechanism or a ball and detent mechanism that may be spring-loaded, orthe like. When the position of one of the recesses 1205 is matched withthe mating mechanism, e.g., the latch or the ball of the ball and detentmechanism, a force is provided for maintaining the striplet 1000specifically in a certain position relative to the analyte meter orother diagnostic medical device, either when lancing or when receivingbody fluid at the sensor 1002. That is, the latch or ball and detentmechanism, or the like, holds the striplet in place for lancing byfitting into one of the recesses 1205, and then when the striplet isappropriately moved, e.g, rotated and/or flipped, so that the sensor canreceive body fluid at the lancing site, the latch or ball and detentmechanism then holds the striplet in place by fitting into the other oneof the recesses 1205, while the latch or the ball and detent mechanismneed not itself move other than the ball sliding along the walls 1203and moving into and out of each slot 1205. In many embodiments, only thestriplet is moved between lancing and testing, such that the meter andthe lancing site relative to the meter may remain stationary while thestriplet is reoriented, e.g., by rotation and/or by being flipped.

As shown in FIGS. 4A-7B, inclusive, and particularly at FIG. 6A, boththe base 1006 and the cover 1008 are substantially rectangular in shape,although other shapes may be used The base 1006 has two major surfaces1006 a, 1006 b and in this substantially rectangular embodiment fouredges 1006 c, 1006 d, 1006 e, and 1006 f. The cover 1008 has two majorsurfaces 1008 a, 1008 b and in this substantially rectangular embodimentfour edges 1008 c, 1008 d, 1008 e, and 1008 f. The base 1006 may includea recess 1010 formed in one edge thereof, and the cover 1008 has arecess 1012 formed in one edge thereof. The surfaces of these recesses1010 and 1012 may bear a hydrophilic material in order to enable thesample of biological liquid to have greater affinity for the recesses1010 and 1012 than if the recesses were not bearing a hydrophilicmaterial. The base 1006 and the cover 1008 may be made from anelectrically non-conducting material, e.g., an insulating material, thatis not capable of carrying substantial electric charge or current.Examples of materials usable include polyesters, polyethylene (both highdensity and low density), polyethylene terephthalate, polycarbonate,vinyls, and the like. The material may be treated with a primer or othersuch coating to improve the adhesion of the electrodes thereon. Incertain embodiments, the base and/or cover is made from a hydrophobicpolymeric material, e.g., “MELINEX” polymer, or the like.

FIG. 6A further illustrates a base 1006 that bears a layer ofelectrically conductive material 1014 on the major surface thereoffacing the cover 1008. Conductive material that may be used includegold, carbon, platinum, ruthenium dioxide, palladium, and conductiveepoxies, such as, for example, ECCOCOAT CT5079-3 Carbon-FilledConductive Epoxy Coating (available from W. R. Grace Company, Woburn,Mass.), Ag/AgCl, Ag/AgBr, as well as other materials known to thoseskilled in the art. For example, the embodiment of FIG. 6A may includeAg/AgCl. For example, this electrically conductive material may functionas a counter electrode or as a dual-purpose reference/counter electrode.The major surface of the cover 1008 facing the base 1006 bears a layerof electrically conductive material 1016 in a first area, which layer ofelectrically conductive material. Any suitable conductive material maybe used, such as described above. For example, the conductive materialmay constitute a working electrode. In certain embodiments, a layer ofelectrically conductive material 1018 may be present in a second area,which layer of electrically conductive material may constitute a triggerelectrode. The major surface of the cover 1008 facing the base 1006 alsobears a layer of non-conductive adhesive 1020 in a first area and layerof non-conductive adhesive 1022 in a second area to bond the cover 1008to the base 1006.

The layers of non-conductive adhesive 1020, 1022 also function to spacethe cover 1008 from the base 1006 so that a channel 1024 running alongthe center of the sensor-containing portion 1002 of the test strip 1000is formed. A layer of electrically conductive adhesive 1026 enables thetransfer of signal from the major surface 1006 a of the base 1006 to themajor surface 1008 b of the cover 1008. The layer of electricallyconductive adhesive 1026 may be made from a pressure-sensitive adhesivedoped with an electrically conductive material, e.g., carbon. The layerof electrically conductive adhesive 1026 may be any suitable thickness,and in certain embodiments, it has a thickness of about 0.002 inch.

At least one electrical passageway 1028 enables the transfer of signalfrom the major surface 1008 b of the cover 1008 to the major surface1008 a of the cover 1008. An electrical passageway is a passagewayformed in the cover 1008. The at least one electrical passageway 1028 isfilled with electrically conductive material, such as, for example, anydescribed herein. In certain embodiments the passageway includes carbon.The benefit resulting from the use of one or more electrical passagewaysis that all of the contact pads 1029 a, 1029 b, 1029 c of thesensor-containing portion 1002 of the test strip 1000 can be positionedon one major surface of the cover 1008 of the test strip 1000.

In many embodiments, the dimensions of the sensor-containing portion1002 of the test strip 1000 are as small as possible in order to reducethe size of the magazine 118 and reduce the volume of sample required tocarry out a test. For example, dimensions of the base 1006 and cover1008 may be approximately 6 mm×6 mm x<2 mm, although other dimensionsmay be used. Dimensions of the electrodes and dimensions of a sampleflow channel 1024 that may be used are described in U.S. Pat. Nos.6,299,757 and 6,616,819. When the sample of biological liquid isintroduced at the sample receiving end, e.g., at hydrophilic recesses1010, 1012, if present, the liquid is easily drawn up into the channel1024, along which the liquid flows by means of capillary attraction. Themajor surface 1008 a of the cover 1008 not facing the base 1006 haselectrical contact pads 1029 a, 1029 b, 1029 c exposed, which electricalcontact pads 1029 a, 1029 b, 1029 c are in contact with the contactleads 1030 a, 1030 b, 1030 c, 1030 d of the carrier 296, as shown inFIG. 7C.

The cover 1008 also has two recesses 1032, 1034 in the edgesperpendicular to the edge having the sample uptake recess 1012. Thefunction of these recesses 1032, 1034 in the sides is to securely attachthe sensor-containing portion 1002 of the test strip 1000 to thelancet-containing portion 1004 of the test strip 1000, which holds thelancet in place. As shown in FIG. 4, the tabs 1036 and 1038 projectdownwardly from the lancet-containing portion 1004 of the test strip1000 toward the recesses 1032, 1034 in the edges of thesensor-containing portion 1002 of the test strip 1000. In certainembodiments, the lancet and strip do not physically contact each other.

As noted above, the striplets may be used with a meter or otherelectrical device having an electrical connector, which is configured tocouple with and contact the contact pads at the end of a sensor, such asdescribed above. A meter for use with the striplets typically includes apotentiostat or other component to provide a potential and/or currentfor the electrodes of the sensor. The meter also typically includes aprocessor (e.g., a microprocessor or hardware) for determining theconcentration of an analyte from the signals from the sensor.

The meter may also include a visual display or port for coupling adisplay to the sensor and/or audio componentry. The display displays thesignals from the sensor and/or results determined for the signals fromthe sensor including, for example, the concentration of an analyte,and/or the exceeding of a threshold of the concentration of an analyte(including, for example, hypo- or hyperglycemia). Furthermore, the metermay be configured to indicate to the user, via, for example, an audible,visual, or other sensory-stimulating alarm, when the level of theanalyte is at or near a threshold level. For example, an alarm systemmay be included. For example, if glucose is monitored then an alarm maybe used to alert the user to a hypoglycemic or hyperglycemic glucoselevel and/or to impending hypoglycemia or hyperglycemia.

The electrical connector employs contact leads that provide electricalconnection between the sensor and the meter. The leads have proximalends to physically contact the contact pads and distal ends to connectto any attached meter. The end of the sensor that has the contact padscan be slid into or mated with the electrical connector by placing thesensor into a slide area, which provides a support for and retains thesensor. It is important that the contact leads of the electricalconnector make electrical contact with the correct pads of the sensor sothat the working electrode and counter electrode(s) are correctlycoupled to the meter. In certain embodiments of the medical diagnosticdevice 100 described herein, the carrier 296 substantially performs theaforementioned functions of the meter that is described in U.S. Pat. No.6,616,819.

In another embodiment, the sensor-containing portion 1002′ includes abase 1006′ and a cover 1008′. As shown in FIGS. 8A-8C, inclusive, boththe base 1006′ and the cover 1008′ are substantially rectangular inshape, but other shapes may be employed. The base 1006′ has two majorsurfaces 1006 a′, 1006 b′ and in this substantially rectangularembodiment four edges 1006 c′, 1006 d′, 1006 e′, and 1006 f. The cover1008′ has two major surfaces 1008 a′, 1008 b′ and in this substantiallyrectangular embodiment four edges 1008 c′, 1008 d′, 1008 e′, and 1008 f.The base 1006′ has optional recess 1010′ formed in one edge thereof, andthe cover 1008′ has a recess 1012′ formed in one edge thereof. Thesurfaces of these recesses 1010′ and 1012′ may bear a hydrophilicmaterial in order to enable the sample of biological liquid to havegreater affinity for the recesses 1010′, 1012′ than if the recesses werenot bearing a hydrophilic material.

The base 1006′ bears a layer of electrically conductive material 1014′(for example, Ag/AgCl) on the major surface thereof facing the coverlayer 1008′. This electrically conductive material functions as a dualpurpose reference/counter electrode. The major surface of the cover1008′ facing the base 1006′ bears a layer of electrically conductivematerial 1016′ in a first area, which layer of electrically conductivematerial constitutes a working electrode, and a layer of electricallyconductive material 1018′ in a second area, which layer of electricallyconductive material constitutes a trigger electrode. The major surfaceof the cover 1008′ facing the base 1006′ also bears a layer ofnon-conductive adhesive 1020′ in a first area and layer ofnon-conductive adhesive 1022′ in a second area to bond the cover 1008′to the base 1006′.

The layers of non-conductive adhesive 1020′, 1022′ also function tospace the cover 1008′ from the base 1006′ so that a channel 1024′running along the center of the sensor-portion 1002′ of the test strip1000′ is formed. A layer of conductive adhesive 1026′ enables thetransfer of signal from the major surface 1006 a′ of the base 1006′ tothe major surface 1008 b′ of the cover 1008′. The layer of electricallyconductive adhesive 1026′ can be made from a pressure-sensitive adhesivedoped with an electrically conductive material, e.g., carbon. The layerof electrically conductive adhesive 1026′ typically has a thickness ofabout 0.002 inch.

At least one electrical passageway 1028′ enables the transfer of signalfrom the major surface 1008 b′ of the cover 1008′ to the major surface1008 a′ of the cover 1008′. An electrical passageway 1028′ is apassageway formed in the cover 1008′. The at least one electricalpassageway 1028′ is filled with electrically conductive material, suchas, any conductive or semiconductive material described herein, forexample, carbon. The benefit resulting from the use of one or moreelectrical passageways is that all of the contacts of thesensor-containing portion of the test strip can be positioned on onemajor surface of the cover of the test strip. The electrical passageways1028′ may be identical to or substantially similar to the electricalpassageways 1028 shown in FIGS. 6A AND 6B.

The dimensions of the sensor-containing portion 1002′ of the test strip1000′ may be any suitable size, and in many embodiments the dimensionsare as small as possible in order to in order to reduce the size of theassembly 110 and reduce the volume of sample required to carry out atest. For example, dimensions of the base 1006′ and cover 1008′ may beabout 6 mm×6 mm x<2 mm. Dimensions of electrodes and channels that maybe used are described in U.S. Pat. Nos. 6,229,757 and 6,616,819. Whenthe sample of biological liquid is introduced at the sample receivingarea, e.g., at hydrophilic recesses 1010′ and 1012′, if present, thesample is easily drawn up into the channel 1024′, along which the sampleflows by means of capillary attraction. The major surface of the cover1008′ not facing the base 1006′ has electrical contact pads 1029 a′,1029 b′, 1029 c′ exposed, which electrical contact pads 1029 a′, 1029b′, 1029 c′ are in contact with the contact leads 1030 a, 1030 b, 1030c, 1030 d of the carrier 296, as shown in FIG. 8C.

The base 1006′ also has two openings 1032′, 1034′ formed therein oneither side of one leg of the L-shaped electrode 1014′. The function ofthese openings 1032′, 1034′ is to securely attach the sensor-containingportion 1002′ of the test strip 1000′ to the lancet-containing portion,which holds the lancet in place. When the sensor-containing portion ofthe test strip has recesses in the sides of the cover, as shown in FIGS.4 and 7A, the tabs of the lancet-containing portion of the test stripproject downwardly, in the manner of the tabs of the lancet-containingportion shown in FIG. 4. When the sensor-containing portion of the teststrip has openings in the base, as shown in FIGS. 8B, 9, and 10, thetabs of the lancet-containing portion of the test strip projectupwardly, in the manner of the tabs of the lancet-containing portionshown in FIG. 9. The test strip 1000′ of this embodiment can employ thesame carrier 296 that can be used with the embodiment of the test strip1000 previously described and the same type of meter as described inU.S. Pat. No. 6,616,819.

In still another embodiment, as shown in FIGS. 9-11, inclusive, a teststrip 1100 comprises a sensor-containing portion 1102 and alancet-containing portion 1104. The sensor-containing portion 1102includes a base 1106 and a cover 1108. The base 1106 is substantiallyrectangular in shape and has two major surfaces 1106 a, 1106 b and fouredges 1106 c, 1106 d, 1106 e, and 1106 f. The base 1106 has a recess1110 formed in one edge thereof. The surface of this recess 1110 bears ahydrophilic material in order to enable the sample of biological liquidto have greater affinity for the recess 1110 than if the recess were notbearing a hydrophilic material.

On one major surface of the base 1106 is a layer of electricallyconductive material 1112 in a first area and a layer of electricallyconductive material 1114 in a second area. The first area constitutesthe working electrode and the second area constitutes the triggerelectrode. The cover 1108 is separated from the base 1106 by layers1116, 1118 of non-conductive adhesive applied to the base 1106 and cover1108 in such a manner that a channel 1120 forming a sample flow path iscreated. This channel 1120 runs along the center of the sensor-portion1102 of the test strip 1100. The cover 1108 is made of an electricallyconductive material (such as, for example, vinyl having an electricallyconductive material, e.g., Ag/AgCl, thereon) and functions as a dualpurpose reference/counter electrode.

When a sample of biological liquid is introduced at the hydrophilicrecess 1110, the sample is easily drawn up into the channel 1116, alongwhich the sample flows by means of capillary attraction. Portions of theelectrically conductive material of the base 1106 function as electricalcontact pads. The base 1106 has two openings 1122, 1124 formed thereinon either side of the cover 1108. The function of these openings 1122,1124 is to securely attach the sensor-containing portion 1102 of thetest strip 1100 to the lancet-containing portion 1104, which holds thelancet in place. This embodiment does not require a conductive adhesiveor electrical passageways to carry out determination of analytes.

The test strip 1100 of this embodiment can employ the same carrier 296that can be used with the embodiments of the test strips 1000, 1000′previously described and the same type of meter as described in U.S.Pat. No. 6,616,819.

FIGS. 10A-10B illustrate embodiments of a lancet body 1202 with a teststrip 1002 coupled thereto and a lancet-containing portion 1004 alsocoupled to the lancet body 1202 in accordance with certain embodiments.The test strip 1002 of FIG. 10A is shown with opposing rectangularcut-outs 1122 a and 1122 b from its sides for coupling with teeth 1136a, 1136 b of the lancet body. In another embodiment which is not shown,only a single tooth and slot are involved, while rotationalstabilization is provided by the configuration of the walls of thelancet body 1202. The test strip fits securely in L-shaped grooves 1290on either side of the lancet body 1202 as illustrated at FIG. 10B.

A lancet 1200 may be integrated directly into the sensor-containingportion 1002, 1002′, 1102 of the test strip. Alternatively, thesensor-containing portion 1002, 1002′, 1102 of the test strip may beattached to the lancet-containing portion of the test strip. The medicaldiagnostic device 100 may have an alignment feature to ensure thatmovement, e.g., rotation, of the test strip during use does not resultin misalignment of the sample application zone of the test strip. Thealignment feature may be provided by springs associated with the carrier296.

The lancet-containing portion 1004 shown in FIG. 4 may be used with, ormay be modified to be used with, any of the sensor-containing portions1002, 1002′, and 1102 described herein. For example, the tabs forconnecting the lancet-containing portion to the sensor-containingportion can be modified to project upwardly to enable thelancet-containing portion to be used with a sensor-containing portionhaving openings in the base, rather than recesses in the sides of thebase and the cover. It should be noted that other embodiments of thelancet-containing portion may be used with any of the sensor-containingportions 1002, 1002′, and 1102 described herein.

As shown in FIG. 4, the lancet-containing portion 1004 is shown ashaving a lancet-containing body 1202. The lancet 1200 is held in thelancet-containing body 1202. The lancet-containing body 1202 may beattached to the sensor-containing portion 1002 by tabs 1036, 1038 or canbe attached to the sensor-containing portion 1002′, 1102 by tabs 1136,1138. When the sensor-containing portion of the test strip has recessesin the sides of the cover, as shown in FIGS. 4 and 7A, the tabs 1036,1038 of the lancet-containing portion of the test strip projectdownwardly, in the manner of the tabs of the lancet-containing portionshown in FIG. 4.

When the sensor-containing portion of the test strip has openings in thebase, as shown in FIGS. 8B, 9, and 10, the tabs 1136, 1138 of thelancet-containing portion of the test strip project upwardly, in themanner of the tabs of the lancet-containing portion shown in FIG. 9. Anysuitable dimensions of the lancet-containing body may be employed, andin certain embodiments dimensions of the lancet-containing body 1202 ofthe lancet-containing portion 1004 are 10 mm×8 mm×1.5 mm. Typicaldimensions of the protective cover 1204 for the lancet 1200 are 3 mm×1.4mm. Typical dimensions of the needle for forming the lancet 1200 are 28to 30 gauge, 10 mm total length, 3.5 mm exposed length.

A lancet 1200 for puncturing the skin to obtain a sample of biologicalliquid includes a sharp metal component (needle) that is maintained in asterile condition until the moment of use. In addition, the lancet 1200is disposable with minimum possibility of an injury subsequent to theinitial use. The lancet 1200 includes a substantially cylindrical needlehaving a sharp end and an opposing end which may be a blunt end. The tip1200 a of the lancet 1200, i.e., the sharp end, may include a protectivecover 1204 that ensures sterility of the lancet 1200. The protectivecover 1204 is also designed to be re-attached to the tip 1200 a of thelancet 1200 for safe disposal. The opposing end (e.g., a blunt end) maybe embedded into the lancet-containing body 1202 by insert molding oradhesive. In one embodiment, the lancet-containing body 1202 includes apolymeric material molded into a substantially rectangular shape.

The tip 1200 a of the lancet 1200 and as much of the lancet 1200 as isexpected to puncture the skin of he patient may be embedded in theprotective cover 1204, e.g., a polymeric plug, e.g., an elastomericplug, such as a thermoplastic elastomeric, silicone, plug. In thisconfiguration, ionizing radiation may be used to sterilize the lancet1200 and the elastomer will prevent subsequent contamination. Embeddingthe piercing portion (tip) 1200 a of the lancet 1200 in a soft materialdoes not damage the delicate tip 1200 a of the lancet 1200 but forms atight seal that allows for sterilization (such as by irradiation) andthe preservation of that sterile condition. Such a protective cover 1204may be removed from the piercing portion of the lancet 1200 either bypulling the protective cover 1204 off the tip 1200 a of the lancet 1200or by fully piercing through the protective cover 1204 and allowing theprotective cover 1204 to cover a more proximal part of the lancet 1200.

The nature of the thermoplastic elastomer (TPE) eliminates the necessityof relocating the tip 1200 a of the used lancet 1200 precisely into thehole originally occupied by the tip 1200 a of the unused lancet 1200.Relocation of the tip 1200 a of the lancet 1200 at any position in thethermoplastic elastomeric protective cover 1204 is sufficient to preventthe tip 1200 a of the lancet 1200 from being exposed after the teststrip is ejected from the medical diagnostic device 100.

Thermoplastic elastomers (TPE) are easily processed rubbery materials.They can be easily formed in various shapes. If a sharp lancet 1200 isembedded into a piece of thermoplastic elastomer, and then irradiated byeither gamma radiation or electron beam radiation of sufficient energy,the lancet 1200 is rendered sterile, and because the thermoplasticelastomer forms a tight seal, the lancet 1200 remains sterile for arelatively long period of time.

If the protective cover 1204 made is made of thermoplastic elastomer,and the thermoplastic elastomer is at least partially enveloped by amore rigid material, the protective cover 1204 acts more like a rigidbody, but keeps the desired features of the thermoplastic elastomer.Configurations of this design might include the lamination ofthermoplastic elastomer between thin layers of rigid plastic or metal orthe coextrusion of thermoplastic elastomer with a more rigid polymer.The cross-section of such a coextruded profile can be circular,rectangular, or any other shape that renders it useful. Such acombination of thermoplastic elastomer and rigid material can beprovided with features such that the combination is allowed to slideproximally on the shaft of the lancet 1200, eventually exposing the tip1200 a of the lancet 1200 for lancing. After the lancet 1200 is used,the subassembly can be slid distally and the connection between theprotective cover 1204 and the lancet 1200 changed such that theprotective cover 1204 cannot return to a position that exposes the tip1200 a of the lancet 1200.

It should be noted that all of the embodiments of the test strip shownherein are characterized by having the tip 1200 a of the lancet 1200 ofthe lancet-containing portion 1004 of the test strip located about 180°from an uptake area, e.g., a recess, of the sensor-containing portion1002, 1002′, 1102 of the test strip. Such positioning renders the teststrips suitable for use with the medical diagnostic device. However, thelancet may be positioned elsewhere with respect to the uptake area.

The test strips and the magazines 118 containing a plurality of teststrips may be made by any suitable process. In certain embodiments, thefollowing process may be employed:

To prepare the lancet-containing portion 1004 of a test strip,unfinished lancets are provided. These unfinished lancets are ground andcut to a suitable dimension, e.g., about 10 mm. The ground, cut lancets1200 are then molded into a plastic body 1202 to form thelancet-containing portion 1004 of the test strip. To prepare thesensor-containing portion 1002, 1002′, 1102 of the test strip, theelectrodes are disposed, e.g., printed, onto the backing or cover, theappropriate reagents are disposed proximate one or more electrodes,e.g., coated over one or more of the electrodes.

Below a sample application well or zone of a test strip may be a wickingmembrane that is striped with various reagents to create variousreagent, capture and/or eluate zones. A hemolysis reagent zone may bepositioned below a sample application zone. The hemolysis reagent zonemay include a hemolysis reagent that is striped, such as absorbed,confined, or immobilized, on a wicking membrane of the test strip. Asmall amount of hemolysis reagent, such as about 1 to about 2 or about 3microliters, for example, is sufficient for striping the wickingmembrane such that the hemolysis reagent zone is sufficiently confinedon the test strip. Any reagent or combination of reagents suitable forhemolysis, and the consequent liberation of hemoglobin, can be used. Byway of example, an ionic detergent, such as sodium dodecyl sulfate(SDS), a non-ionic detergent, such as a octylphenol ethylene oxidecondensate or octoxynol-9 or t-octylphenoxypolyethoxy-ethanol, soldunder the name, Triton X-100, and commercially available from SigmaChemical or Sigma-Aldrich Co., or a hypotonic solution, may be used as ahemolysis reagent.

A glycated hemoglogin capture zone may be disposed downstream relativeto the hemolysis zone. By way of example, any chemical reagentcomprising at least one boron ligand, such as phenyl boronate or otherboron affinity chemistry used in the above-referenced Glycosal test, orsuch as m-aminophenylboronic acid, such as that of a gel that isimmobilized on cross-linked, beaded agarose, any antibody, such asanti-HbA1c antibody available from a number of sources, any immunoassayreagent, any chemical reagent including at least one binding ligand,such a boronic acid involving boron binding ligands, and the like, andany combination thereof, that is suitable for the binding of glycatedhemoglobin to the capture zone 222, such as via covalent bonds, forexample, or the capture of glycated hemoglobin in capture zone 222, maybe used. A hemolysis layer/zone and a glycated hemoglobin capture zonecan be integrated to form an integrated reagent zone.

The cards of sensor-containing portions 1002, 1002′, 1102 are singulatedto form individual sensor-containing portions 1002, 1002′, 1102. Theindividual sensor-containing portions 1002, 1002′, 1102 are combinedwith the lancet-containing portions 1004 to form completed test strips.Pluralities of test strips are then loaded into assembly 110 (see FIG.1).

The sensors described herein may be configured for analysis of ananalyte in a small volume of sample by, for example, coulometry,amperometry, and/or potentiometry. The sensors may also be configuredfor optical analysis. The sensors may be configures to determine analyteconcentration in about 1 μL or less of sample, e.g., 0.5 μL or less ofsample e.g., 0.2 μL or less of sample e.g., 0.1 μL or less of sample.The chemistry of the sensors generally includes an electron transferagent that facilitates the transfer of electrons to or from the analyte.One example of a suitable electron transfer agent is an enzyme whichcatalyzes a reaction of the analyte. For example, a glucose oxidase orglucose dehydrogenase, such as pyrroloquinoline quinone glucosedehydrogenase (PQQ), may be used when the analyte is glucose. Otherenzymes may be used for other analytes. Additionally to or alternativelyto the electron transfer agent, may be a redox mediator. Certainembodiments use a redox mediator that is a transition metal compound orcomplex. Examples of suitable transition metal compounds or complexesinclude osmium, ruthenium, iron, and cobalt compounds or complexes. Inthese complexes, the transition metal is coordinatively bound to one ormore ligands, which are typically mono-, di-, tri-, or tetradentate. Theredox mediator may be a polymeric redox mediator or a redox polymer(i.e., a polymer having one or more redox species). Examples of suitableredox mediators and redox polymers are disclosed in U.S. Pat. Nos.6,338,790; 6,229,757; 6,605,200 and 6,605,201.

The sensor also includes a sample chamber to hold the sample inelectrolytic contact with the working electrode. In certain embodiments,the sample chamber may be sized to contain no more than about 1 μl_ofsample, e.g., no more than about 0.5 μL, e.g., no more than about 0.2μL, e.g., no more than about 0.1 μL of sample.

U.S. Pat. No. 6,229,757 also discloses materials for preparing a workingelectrode, a counter electrode, a dual purpose reference/counterelectrode, a reference electrode, analytes that may be determined,examples of redox mediators, examples of second electron transferagents, and details of sample chamber. The teachings of U.S. Pat. No.6,299,757 may be used to prepare the components of the sensor-containingportion of the test strips.

The assemblies 110 of FIG. 1 may be prepared by first molding thedesiccants into platforms. Resilient biasing elements and the platformsare then assembled into the housings of the assemblies 110. Theassemblies 110 are then packed and shipped.

Operation

Embodiments for operating the medical diagnostic device to dispense atest strip, form an opening in the skin of a patient to obtain a sampleof biological liquid, collect a sample of biological liquid from thepatient, analyze the sample of biological liquid collected from thepatient, and dispose of the used test strip will now be summarized. FIG.12 also depicts operational processes in a flow chart for certainembodiments. Embodiments may include fewer than all of that which isshown, and other may include further processes.

After the test strip 1000 has been fed into the cradle 280, the medicaldiagnostic device 100 causes the test strip 1000 to be oriented in sucha manner that the lancet 1200 of the lancet-containing portion 1004 ofthe test strip 1000 may be introduced into the skin of a patient to forman opening in the skin of the patient. In certain embodiments, such anorientation is carried out by a motor. In these embodiments, a PCBassembly may be programmed so that orientation is carried out accuratelyand reliably.

Such an orientation may be carried out by having the transmission systemrotate the cradle 280 of the lancing/collecting assembly, e.g., about90° (clockwise or counterclockwise), so that the tip 1200 a of thelancet 1200 faces an opening in an end cap, so that when the medicaldiagnostic device 100 is placed against the skin of the patient, the tip1200 a of the lancet 1200 will be facing the skin of the patient.

The medical diagnostic device 100 then causes the test strip 1000 to beoriented in such a manner that the sensor-containing portion 1002 of thetest strip 1000 may be placed in contact with the sample of biologicalliquid emerging from the opening in the skin of the patient. For thisstep, the cradle 280 is rotated about 180° in certain embodiments sothat the sensor-containing portion 1002 of the test strip 1000 contacts,e.g., directly overlies, the biological liquid.

The sample of biological liquid enters the sample application zone ofthe sensor-containing portion 1002 of the test strip 1000, i.e., therecesses 1010, 1012 formed in an edge of the test strip 1000. The sampleof biological liquid travels along the sample flow channel 1024 to thearea where the reagents are disposed. The appropriate reaction occurs,thereby activating the electronics and bringing about a reading of theconcentration of the analyte, which reading is shown in the display. Ifinsufficient quantity of the sample of biological liquid is drawn in theinitial lancing, the user can actuate a retesting procedure beforeactuating the analyzing, whereby the test is aborted so that the usercan re-arm the lancing mechanism and begin again.

The sensor-containing portion 1002 of the test strip 1000 collects asufficient quantity of sample of biological liquid to allow analysis ofthe sample of biological liquid. After a sufficient amount of sample ofbiological liquid is collected, the carrier 296, the electricalcomponents of which are in electrical contact with the contacts of thesensor-containing portion 1002 of the test strip 1000, measures thequantity of analyte in the sample by an electrochemical analyzer. Bythis process, the sample of biological liquid is analyzed to determineat least one characteristic of the sample of biological liquid.

After the sample of biological liquid is analyzed, the protective coverif provided 1204 is automatically re-attached to the tip 1200 a of thelancet 1200 of the lancet-containing portion 1004 of the test strip1000. After the protective cover 1204 is re-attached, the re-coveredtest strip 1000 is ejected from a port in the housing (not shown), e.g.,automatically.

FIG. 12 is a flow chart that illustrates embodiments of a method inaccordance with certain embodiments. As shown in FIG. 12, in thisembodiment there are five basic components of the method. Component 0 ofFIG. 12 involves advancing the test strip from the assembly 110 into thecradle 280, removing the protective cover 1204 from the lancet 1200, androtating the cradle 280 to position the lancet 1200 for entering theskin of the patient. It should be noted that the protective cover 1204could be removed from the lancet 1200 prior to rotating the cradle 280into position for lancing. Component 1 of FIG. 12 involves arming andtriggering the lancet 1200. Component 2 of FIG. 12 involves indexing thetest strip so that the sensor portion of the test strip can obtain bloodfrom the opening formed in the skin in Component 1. Component 3 of FIG.12 involves collecting blood from the opening formed in the skin inComponent 1. Component 4 of FIG. 12 involves reattaching the protectivecover 1204 to the lancet 1200 and ejecting the used test strip from themedical diagnostic device 100.

FIG. 13A through FIG. 13M, inclusive, illustrate in schematic form oneway of carrying out the method of FIG. 12. For the sake ofsimplification, the test strip will be the test strip shown in FIG. 4.Other test strips described can be used in place of the test strip shownin FIG. 4. FIG. 13A shows a test strip 1000 in the assembly 110. FIG.13B shows the test strip 1000 advanced from the assembly 110 andinserted into the lancing/collecting assembly, which is representedschematically by two parallel upright elements, each element having aslot formed therein. FIG. 13C shows the protective cover 1204 beingremoved from the lancet 1200 of the test strip 1000. It should be notedthat the protective cover 1204 could be removed before the test strip1000 is inserted into the lancing/collecting assembly.

FIG. 13D shows the test strip 1000 rotated about 90° so that the lancet1200 is in position for lancing the skin of the patient. FIG. 13E showsthat the lancet 1200 has entered the skin of the patient. FIG. 13F showsthat the lancet 1200 has been retracted from the skin of the patient.FIG. 13G shows that the test strip 1000 is being rotated about 180° sothat the sensor-containing portion 1002 can collect biological liquidemerging from the opening formed in the skin of the patient. FIG. 13Hshows that the sensor-containing portion 1002 of the test strip 1000 isready to be indexed so that the sensor-containing portion 1002 cancollect biological liquid emerging from the opening formed in the skinof the patient.

FIG. 13I shows the sensor-containing portion 1002 of the test strip 1000contacting the biological liquid emerging from the skin of the patient.FIG. 13J shows that the test strip 1000 is being rotated about 90° sothat the test strip 1000 will come into the proper in position for beingejected from the medical diagnostic device. FIG. 13K shows the teststrip 1000 in position for ejection from the medical diagnostic device100. FIG. 13L shows the protective cover 1204 being reattached to thelancet 1200. FIG. 13M shows the test strip 1000 being ejected from themedical diagnostic device 100.

Alternative Embodiments

The monitoring apparatuses are configured for analysis (e.g.,concentration determination) of an analyte in a sample of body fluid,where in certain embodiments the apparatuses are configured to determinethe concentration of an analyte in a small volume of sample, e.g., lessthan about 1 microliter, e.g., less than about 0.5 microliters, e.g.,less than about 0.2 microliters, e.g., about 0.1 microliters or less.The monitoring apparatuses may be configured for analysis of an analytein a volume of sample by, for example, coulometry, amperometry, and/orpotentiometry. In certain embodiments, the monitoring apparatuses areconfigured for optical analysis of an analyte in a sample.

A striplet includes both a test strip portion and a lancet portion.These may be relatively opposed, e.g., extending about 180 degrees fromeach other, or extending at another angle from zero to 360 degrees. Thelancet portion may couple to the test strip portion as a two-piecedevice, or each may couple with a lancet body as a three-piece device.

In an alternative embodiment, a medical diagnostic device is providedthat carries out the functions of:

-   -   (f) storing a plurality of lancets and sensors;    -   (g) feeding a plurality of lancets and sensors to a system that        employs a lancet to form an opening in the skin of a patient and        then employs the sensor to collect a sample of biological liquid        that emerges from the opening formed in the skin;    -   (h) forming an opening in the skin of the patient by means of        the lancet;    -   (i) collecting the sample of biological liquid emerging from the        opening formed in the skin of the patient by means of the        sensor;    -   (j) analyzing the sample of biological liquid collected by the        sensor; and    -   (k) ejecting the used lancet and the used sensor in a safe        manner.

In a further embodiment, a test strip includes a lancet-containingportion and a sensor-containing portion. During the time that the teststrip is stored in the medical diagnostic device, a protective coverencloses the lancet of the lancet-containing portion. The medicaldiagnostic device is capable of removing the protective cover to enablethe lancet to form an opening in the skin of the patient and is furthercapable of re-attaching the protective cover onto the lancet to enablethe medical diagnostic device to eject the used test strip in a safemanner.

In another embodiment, a lancing/collecting assembly receives a teststrip that includes both a lancet-containing portion and asensor-containing portion. By means of various operations, thelancing/collecting assembly is configured to (a) orient thelancet-containing portion of the test strip in such a manner that thelancet of the lancet-containing portion of the test strip can beadvanced toward a lancing and testing site on the skin of the patient inorder to form an opening therein, (b) arm the lancet of thelancet-containing portion of the test strip, (c) trigger the armedlancet of the lancet-containing portion of the test strip so that thelancet forms an opening in the skin of the patient at the lancing andtesting site, (d) orient the sensor-containing portion of the test stripin such a manner that the sensor-containing portion of the test stripcan be advanced toward the opening formed in the skin of the patient tocollect a sample of biological liquid emerging from the opening in theskin of the patient at the lancing and testing site which remainsproximate to a lancing and testing port of an analyte, e.g., glucose,monitoring apparatus; and (e) advance the sensor of thesensor-containing portion of the test strip so that sufficient quantityof the sample of biological liquid can be collected for analysis todetermine a parameter of the biological liquid, e.g., a body analyte,e.g., glucose, level.

The lancing/collecting assembly may also incorporate an analyzer that iscapable of analyzing the sample of biological liquid collected from theopening in the skin of the patient.

In another embodiment, a storing/dispensing assembly is provided for aplurality of test strips, each of which includes a lancet-containingportion and a sensor-containing portion.

In a further embodiment, a method for using a medical diagnostic deviceincludes:

-   -   (a) feeding one of multiple test strips, each of the test strips        having a lancet-containing portion and a sensor-containing        portion, to a lancing/collecting assembly that employs a lancet        of the lancet-containing portion to form an opening in the skin        of a patient, and then employs a sensor of the sensor-containing        portion to collect a sample of biological liquid that emerges        from the opening formed in the skin;    -   (b) forming an opening in the skin of the patient by means of a        lancet in the lancet-containing portion;    -   (c) collecting a sample of biological liquid emerging from the        opening formed in the skin of the patient by means of the sensor        of the sensor-containing portion;    -   (d) analyzing the sample of biological liquid collected by the        sensor of the sensor-containing portion; and    -   (e) ejecting the used test strip in a safe manner.

A medical diagnostic device of an embodiment can perform a plurality ofdiagnostic tests, e.g., 25 tests, before the device requires refillingwith test strips. The medical diagnostic device can perform thefunctions of storing and dispensing test strips, lancing the skin of apatient, collecting a sample of biological liquid, analyzing the sampleof biological liquid collected, and disposing of used test strips. Inthe case of collection of an inadequate quantity of sample, the medicaldiagnostic device enables re-lancing.

In accordance with another embodiment, a medical diagnostic devicerequires only a small volume of sample to carry out a complete test,e.g., 0.3 microliter (see, e.g., U.S. Pat. Nos. 7,058,437, 6,618,934,6,591,125 and 6,551,494, which are hereby incorporated by reference).

The test strip combines a lancet and a sensor in a single small unit.After the skin of the patient is pierced and a sample of biologicalliquid, e.g., blood, appears, the test strip is moved into position forcollecting a sample of the liquid, and the liquid enters the sampleapplication zone of the sensor-containing portion of the test stripwithout manipulation of the test strip by the user.

The striplet is also small in size. Generally the striplet is less than2 mm×less than 1 mm×less than 0.3 mm, and in some embodiments, less than1.5 mm×less than 0.75 mm×less than 0.2 mm, e.g., approximately 1 mm×0.5mm×0.1 mm.

The striplet is advantageously ideal for alternative site testing, i.e.,away from the fingertips, where smaller amount of blood are availablethan at the fingertips, such as less than 1 microliter, and even lessthan 0.5 microliters, or less than 0.3 microliters, or less than 0.2microliters, or even 0.1 microliters (100 nanoliters). See for exampleU.S. Pat. No. 6,284,125 which describes this feature in more detail andin incorporated by reference.

Embodiments include calibration in one or more schemes. A calibrationmodule, whether it be a bar code, a RFID tag, a label, or otherwise maybe located on a striplet and/or on a striplet container. U.S.application Ser. No. 11/350,398, which is assigned to the same assigneeand incorporated by reference, provides further examples. There may becontact pads that may be shorted together or kept apart during the teststrip manufacturing process in order to communicate a calibration codeto the meter. There may be a set of contact pads and a varyingresistance between the two pads where the resistance is changed duringthe manufacturing process of the test strip to communicate a calibrationcode to the meter. There may be an electrical memory that is readableand writable by the meter, which communicates a calibration code to themeter. A calibrator can carry other information such as stripletexpiration and/or a striplet number count down.

Various modifications and alterations of this invention will becomeapparent to those skilled in the art without departing from the scopeand spirit of this invention, and it should be understood that thisinvention is not to be unduly limited to the illustrative embodimentsset forth herein, which may be amended or modified or elements thereofcombined without departing from the scope of the present invention,which is as set forth in the appended claims including structural andfunctional equivalents thereof.

In methods that may be performed according to embodiments herein andthat may have been described above and/or claimed below, the operationshave been described in selected typographical sequences. However, thesequences have been selected and so ordered for typographicalconvenience and are not intended to imply any particular order forperforming the operations. Additionally, some parts of a sequence may beomitted and/or added in certain embodiments.

In addition, all references cited above herein, in addition to thebackground and summary of the invention sections, are herebyincorporated by reference into the detailed description of theembodiments as disclosing alternative embodiments and components.

1-90. (canceled)
 91. An integrated lancet and testing strip formeasuring a body analyte level, comprising: a flat lancet body having atop side, a bottom side opposite the top side, a test strip receivingend, and a lancet receiving end opposite the test strip receiving end,wherein the test strip receiving end comprises a first protruding armspaced apart from a second protruding arm, the first protruding arm andthe second protruding arm forming an opening on the top side of thelancet body, the opening flanked by the first and second protrudingarms; a lancet needle protruding from the lancet end of the lancet body;and a test strip coupled to the test strip receiving end of the lancetbody and disposed between the first and second protruding arms, the teststrip comprising: multiple electrodes and assay chemistry for testingthe body analyte level of an applied body fluid; contacts forelectrically coupling to a meter disposed on a surface of the test stripat the test strip receiving end of the lancet body, wherein the contactsare disposed on the test strip between the first and second protrudingarms such that the contacts are exposed through the opening on the topside of the lancet body; and a sample receiving portion disposed at adistal edge of the test strip such that the sample receiving portion isat an opposite end of integrated lancet and test strip than the lancetneedle; wherein the integrated lancet and testing strip is configuredfor lancing and application of body fluid at a lancing site byautomatically lancing, withdrawing, reorienting and re-advancing theintegrated lancet and testing strip.
 92. The integrated lancet andtesting strip of claim 91, wherein the test strip is coupled to the teststrip receiving end of the lancet body such that a first portion of thetest strip is disposed between the first and second protruding arms anda second portion of the test strip is disposed outside the first andsecond protruding arms of the lancet body, and wherein the samplereceiving portion is disposed on the second portion of the test strip.93. The integrated lancet and testing strip of claim 91, wherein teststrip is disposed within L-shaped grooves in the first and secondprotruding arms.
 94. The integrated lancet and testing strip of claim91, wherein the test strip comprises first and second openings to securethe test strip to the lancet body.
 95. The integrated lancet and testingstrip of claim 94, wherein the first opening in the test strip securesto a first tab of the first protruding arm of the lancet body, and thesecond opening in the test strip secures to a second tab of the secondprotruding arm of the lancet body.
 96. The integrated lancet and testingstrip of claim 94, wherein the first opening in the test strip securesto a first tab on the lancet body, and the second opening in the teststrip secures to a second tab on the lancet body, wherein the first taband the second tab are disposed on the bottom side of the lancet body infacing relation to the opening in the top side of the lancet body. 97.The integrated lancet and testing strip of claim 91, wherein the lancetneedle and test strip are separated such as not to be in fluidcommunication with regard to the body fluid.
 98. The integrated lancetand testing strip of claim 91, wherein the lancet body comprises a pairof relatively disposed recesses for respectively positioning the teststrip for lancing and application of body fluid at said samelancing/testing site.
 99. The integrated lancet and testing strip ofclaim 98, wherein each of said pair of recesses comprises asubstantially trapezoidal shape.
 100. The integrated lancet and testingstrip of claim 98, wherein the recesses are configured for coupling witha spring-loaded ball and detent mechanism.
 101. The integrated lancetand testing strip of claim 98, wherein the recesses are configured forcoupling with a latching mechanism.
 102. The integrated lancet andtesting strip of claim 91, further comprising a lancet cap for securingthe protruding lancet needle.
 103. The integrated lancet and testingstrip of claim 91, wherein the test strip comprises a base and a cover.104. The integrated lancet and testing strip of claim 103, wherein thecover has a working electrode applied to one or more major surfacesthereof.
 105. The integrated lancet and testing strip of claim 104,further comprising a trigger electrode.
 106. The integrated lancet andtesting strip of claim 105, wherein the sample receiving portioncomprises a recess formed in an edge of the base or the cover, or both.107. The integrated lancet and testing strip of claim 106, wherein therecess has a hydrophilic material applied thereto.
 108. The integratedlancet and testing strip of claim 106, wherein said lancet needle ispositioned approximately 180° from said recess.